Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload

NCT01254227 | Completed Phase 2 Results

• 2 other identifiers: CICL670A22142010-021062-29
• Study Type: interventional
• Target: 60
• Locations: 8 countries
• Sites: 15

Brief Summary

This study will evaluate the efficacy and safety of deferasirox in combination with deferoxamine followed be deferasirox monotherapy in patients with severe iron overload due to chronic blood transfusions.

Conditions

Cardiac Iron Overload

Keywords

Cardiac iron overload,; deferasirox,; deferoxamine

Outcome Measures

Primary Outcomes (1)

• Change in Cardiac Iron Content From Baseline to Month 12

  Cardiac T2\* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2\* value of \<10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2\* or do not have any post-baseline T2\* are excluded from the analysis.

  From Baseline to Month 12

Secondary Outcomes (6)

• Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24

  From the Months 6, 12, 18 and 24

• Change in Cardiac Iron Content From Baseline to Month 6,18 and 24

  From Baseline to Months 6, 18 and 24

• Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24

  From the Months 6, 12, 18 and 24

• Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24

  From the Months 6, 12, 18 and 24

• Time to Achieve From Baseline (FAS) of at Least 10% at Month 24

  At 24 months

Study Arms (1)

Deferasirox

EXPERIMENTAL

Deferoxamine combination followed by Deferasirox monotherapy

Drug: Deferasirox and Deferoxamine

Interventions

Deferasirox and Deferoxamine DRUG

Deferasirox

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with β-thalassemia major or Diamond-Blackfan anemia (DBA) or congenital sideroblastic anemia on chronic transfusion therapy
• Myocardial T2\* value that is ≥ 5 and \< 10 ms
• Left ventricular ejection fraction (LVEF) ≥ 56% as determined by Magnetic resonance imaging (MRI)
• Liver Iron Concentration (LIC) ≥ 7 mg Fe /g dw as determined by R2 MRI.
• Lifetime history of at least 50 units of red blood cell transfusions, and must be receiving at least ≥ 8 units/yr of red blood cell transfusions
• Serum ferritin ≥ 1000 ng/mL

You may not qualify if:

• Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)
• Patients unable to undergo study assessments including MRI
• Patients with serum creatinine greater than Upper limit of normal ULN)range or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥1.0 mg/mg in a non-first void urine sample at baseline.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Toronto, Ontario, M5G 2C4, Canada

Location

Novartis Investigative Site

Cairo, Egypt

Location

Novartis Investigative Site

Athens, GR, GR-115 27, Greece

Location

Novartis Investigative Site

Patra - RIO, GR, 265 04, Greece

Location

Novartis Investigative Site

Cagliari, CA, 09121, Italy

Location

Novartis Investigative Site

Genova, GE, 16128, Italy

Location

Novartis Investigative Site

Napoli, 80138, Italy

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

London, NW1 2BU, United Kingdom

Location

Related Publications (1)

• Aydinok Y, Kattamis A, Cappellini MD, El-Beshlawy A, Origa R, Elalfy M, Kilinc Y, Perrotta S, Karakas Z, Viprakasit V, Habr D, Constantinovici N, Shen J, Porter JB; HYPERION Investigators. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload. Blood. 2015 Jun 18;125(25):3868-77. doi: 10.1182/blood-2014-07-586677. Epub 2015 May 1.

  PMID: 25934475 DERIVED

Related Links

• link to the results

MeSH Terms

Interventions

Deferasirox; Deferoxamine

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: December 6, 2010
• Study Start: January 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 26, 2021
• Results First Posted: June 24, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); GR (2); TW (1); EG (1); TU (4); CA (1); TH (2); IT (3)